Clinical outcome and biomarker assessments of a multi-centre phase II trial assessing niraparib with or without dostarlimab in recurrent endometrial carcinoma
Madariaga, Ainhoa (Universitat Autònoma de Barcelona)
Garg, Swati (University Health Network, Toronto, Canada)
Tchrakian, Nairi (University Health Network, Toronto, Canada)
Dhani, Neesha C. (University of Toronto, Canada)
Jimenez, Waldo (Juravinski Cancer Centre, Hamilton, Canada)
Welch, Stephen (London Health Sciences Center, London, Canada)
MacKay, Helen (Odette Cancer Centre. Sunnybrook Health Sciences Centre, Toronto, Canada)
Ethier, Josee-Lyne (Kingston Health Sciences Cancer Centre, Kingston, Canada)
Gilbert, Lucy (Royal Victoria Hospital, Montréal, Canada)
Li, Xuan (University Health Network, Toronto, Canada)
Rodriguez, Angela (University Health Network, Toronto, Canada)
Chan, Lucy (University Health Network, Toronto, Canada)
Bowering, Valerie (University Health Network, Toronto, Canada)
Clarke, Blaise (University Health Network, Toronto, Canada)
Zhang, Tong (University of Toronto, Canada)
King, Ian (University of Toronto, Canada)
Downs, Gregory (University of Toronto, Canada)
Stockley, Tracy (University of Toronto, Canada)
Wang, Lisa (University of Toronto, Toronto, Canada)
Udagani, Smitha (University Health Network, Toronto, Canada)
Oza, Amit M. (University of Toronto, Canada)
Lheureux, Stephanie (University of Toronto, Canada)

Data:	2023
Resum:	This multi-centre, non-randomized, open-label, phase II trial (NCT03016338), assessed niraparib monotherapy (cohort 1, C1), or niraparib and dostarlimab (cohort 2, C2) in patients with recurrent serous or endometrioid endometrial carcinoma. The primary endpoint was clinical benefit rate (CBR), with ≥5/22 overall considered of interest. Secondary outcomes were safety, objective response rate (ORR), duration of response, progression free survival and overall survival. Translational research was an exploratory outcome. Potential biomarkers were evaluated in archival tissue by immunohistochemistry and next generation sequencing panel. In C1, 25 patients were enrolled, and CBR was 20% (95% CI: 9-39) with median clinical benefit duration of 5. 3 months. The ORR was 4% (95% CI: 0-20). In C2, 22 patients were enrolled, and the CBR was 31. 8% (95% CI: 16-53) with median clinical benefit duration of 6. 8 months. The ORR was 14% (95% CI: 3-35). No new safety signals were detected. No significant association was detected between clinical benefit and IHC markers (PTEN, p53, MMR, PD-L1), or molecular profiling (PTEN, TP53, homologous recombination repair genes). In conclusion, niraparib monotherapy did not meet the efficacy threshold. Niraparib in combination with dostarlimab showed modest activity.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Biomarkers ; Endometrial Neoplasms ; Female ; Humans ; Neoplasm Recurrence, Local
Publicat a:	Nature communications, Vol. 14 (2023) , art. 1452, ISSN 2041-1723

DOI: 10.1038/s41467-023-37084-w
PMID: 36922497

11 p, 1.2 MB

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